In vivo fates of degradable poly(β-malic acid) and of its precursor, malic acid

To determine whether degradation could influence the in vivo elimination pattern of poly(beta-malic acid) in mice, radioactive urinary excretion and (CO2)-C-14 expiration were studied after intravenous injection of C-14-radiolabeled poly(beta-malic acid) and of its precursor, C-14-malate. The precursor administration led to rapid (CO2)-C-14 exhalation, and only negligible urinary elimination. The reverse was observed for the polymer. It was concluded that: (i) the in vivo degradation of poly(beta-malic acid) chains, if any during the 24-h period of the study, did not release detectable malate molecules, (ii) the large urinary excretion of poly(beta-malic acid) was due to the molar masses being less than the renal filtration threshold, (iii) the degradation of the poly(beta-malic acid) chains in blood was slow enough to allow the fraction with higher molar masses to enter the interstitial space of the tissues, and possibly cells.